PROTEIN CONTROL OF HEME REACTIVITY

血红素反应性的蛋白质控制

• 批准号: 3153708
• 负责人: James Robert Kincaid
• 金额: $ 6.03万
• 依托单位: MARQUETTE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-07-01 至 1986-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3153708
• 关键词: Raman spectrometry; chemical structure function; circular dichroism; heme; infrared spectrometry; ligands; nuclear magnetic resonance spectroscopy; oxygen transport; porphyrin metabolism

Heme proteins are involved in a large number of physiologically important processes, including: delivery of oxygen to the tissues; derivation of stored energy from oxidation of nutrients; protective destruction of potentially dangerous peroxides; and activation and elimination of toxic pollutants and carcinogens. Despite this remarkable functional diversity, all of these species employ the heme group as the active component. Identification of the factors responsible for this varied function would be of obvious benefit for attaining an understanding of the behavior in normal and abnormal states. The long term objective of this research program is the elucidation of the molecular mechanisms by which these various proteins interact with the common heme group to effectively regulate its reactivity. Basically, our approach is to systematically perturb the structure of the heme group and quantitatively determine the functional consequences using appropriate methodology. The equilibria and kinetics of ligand binding to oxygen transport proteins will be investigated using stopped-flow instrumentation and a continuous oxygenation curve analyzer. Commonly accepted enzyme assays will be used to characterize the function of modified derivatives of other heme proteins to be studied. In order to elucidate the molecular basis of altered function, a number of powerful spectroscopic techniques will be used to probe key interactions between the heme and protein and to determine the effect of the structural perturbation on the electronic structure and reactivity of the active site. Spectroscopic methods to be used include: resonance Raman, nuclear magnetic resonance (NMR), infrared, circular dichroism (CD) and electronic absorption spectroscopy. This multifaceted approach, which utilizes a variety of techniques, applied to systematically modified proteins represents a realistic attempt to elucidate the important molecular control mechanisms responsible for such remarkable functional diversity.

血红素蛋白参与大量具有重要生理意义的过程 过程，包括： 向组织输送氧气；的推导 通过营养物质的氧化储存能量；保护性破坏 有潜在危险的过氧化物；以及有毒物质的激活和消除 污染物和致癌物。 尽管具有显着的功能多样性， 所有这些物种都采用血红素基团作为活性成分。 确定导致这种不同功能的因素是 对于理解正常人的行为有明显的好处 和异常状态。 该研究计划的长期目标是 阐明这些不同蛋白质的分子机制 与常见血红素基团相互作用，有效调节其 反应性。 基本上，我们的方法是系统地扰乱 血红素基团的结构并定量确定其功能 使用适当的方法产生的后果。 平衡和动力学 将使用以下方法研究配体与氧转运蛋白的结合 停流仪器和连续氧合曲线分析仪。 普遍接受的酶测定将用于表征功能 待研究的其他血红素蛋白的修饰衍生物。 为了 阐明功能改变的分子基础，许多强大的 光谱技术将用于探测之间的关键相互作用 血红素和蛋白质并确定结构扰动的影响 活性位点的电子结构和反应性。 使用的光谱方法包括：共振拉曼、核 磁共振 (NMR)、红外、圆二色性 (CD) 和电子 吸收光谱。 这种多方面的方法利用了 应用于系统修饰蛋白质的多种技术 代表了阐明重要分子控制的现实尝试 造成这种显着功能多样性的机制。